Nucleosome contact triggers conformational changes of Rpd3S driving high-affinity H3K36me nucleosome engagement

Chun Ruan, Chul Hwan Lee, Haochen Cui, Sheng Li, Bing Li

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The Rpd3S histone deacetylase complex utilizes twosubunits, Eaf3 and Rco1, to recognize nucleosomes methylated at H3K36 (H3K36me) with high affinity and strong specificity. However, the chromobarrel domain of Eaf3 (CHD) that is responsible for H3K36me recognition only binds weakly and with little specificity to histone peptides. Here, using deuterium exchange mass spectrometry (DXMS), we detected conformational changes of Rpd3S upon its contact with chromatin. Interestingly, we found that the Sin3-interacting domain of Rco1 (SID) allosterically stimulates preferential binding of Eaf3 to H3K36-methylated peptides. This activation is tightly regulated by an autoinhibitory mechanism to ensure optimal multivalent engagement of Rpd3S with nucleosomes. Lastly, we identified mutations at the interface between SID and Eaf3 that do not disrupt complex integrity but severely compromise Rpd3S functions invitro and invivo, suggesting that the nucleosome-induced conformational changes are essential for chromatin recognition.

Original languageEnglish (US)
Pages (from-to)204-215
Number of pages12
JournalCell Reports
Volume10
Issue number2
DOIs
StatePublished - Jan 13 2015

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Nucleosomes
Chromatin
Peptides
Histone Deacetylases
Deuterium
Histones
Mass spectrometry
Mass Spectrometry
Chemical activation
Mutation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Nucleosome contact triggers conformational changes of Rpd3S driving high-affinity H3K36me nucleosome engagement. / Ruan, Chun; Lee, Chul Hwan; Cui, Haochen; Li, Sheng; Li, Bing.

In: Cell Reports, Vol. 10, No. 2, 13.01.2015, p. 204-215.

Research output: Contribution to journalArticle

Ruan, Chun ; Lee, Chul Hwan ; Cui, Haochen ; Li, Sheng ; Li, Bing. / Nucleosome contact triggers conformational changes of Rpd3S driving high-affinity H3K36me nucleosome engagement. In: Cell Reports. 2015 ; Vol. 10, No. 2. pp. 204-215.
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